By Sean Firoz, Senior Executive, Communications & External Relations
Imagine being genetically screened at birth, a screening that determines your fate for life. To maintain peace and harmony in the world, you are to live in the faction with people who have the same genetic traits.
This is the dystopian world of Divergent, a trilogy of young adult novels by American writer Veronica Roth. Like in her imagined post-apocalyptic future, fiction - whether in novels and movies - has often cast genetic testing in an ugly light. However, thanks to the rapid advances in technology and in our understanding of the interplay between genes, lifestyle and the environment, we are on the cusp of a world where healthcare can be tailored to each individual and many chronic diseases such as diabetes and heart disease, can be prevented.
Genes and me
The earliest form of genetic testing can be traced back to the 1960s, when Dr Robert Guthrie developed a screening test for newborns to detect Phenylketonuria (PKU), an “inborn error of metabolism” that predicts whether a child develops mental retardation. The procedure involved a drop of blood taken from the heel of an infant, which informs parents whether their child will develop PKU. Today, genetic testing can detect more than 3,000 rare and common conditions from Huntington disease to Cystic Fibrosis, providing a database for scientists and clinicians to refer to and search for the most effective treatment.
With these remarkable developments in genetic testing, are genes a viable way of predicting our future health?
According to LKCMedicine Associate Professor of Human & Microbial Genetics Eric Yap, by simply looking up the pedigree pattern or family history of a person, one can predict the likelihood of that person developing certain hereditary diseases.
“Genetic prediction preceded the molecular era. For instance, if a mother who has had a son deficient for G6PD (glucose-6-phosphate dehydrogenase, an enzyme that keeps the red blood cells healthy), we can predict an approximate 50% chance that the next male child will also lack the enzyme."
While pedigree analysis has helped doctors figure out the probability of a newborn child developing hereditary diseases, today it is possible, through molecular genetic testing, to determine precisely whether the baby is affected and what the exact mutation is. This form of genetic testing is particularly useful for disorders that are caused by a single gene, and despite there being more than 6000 of these Mendelian (a theory of genetic inheritance developed by Austrian Scientist Gregor Mendel) diseases, most are rare or infrequent. The most common ones in Asian populations are the red blood cell disorders such as Thalassemia and G6PD deficiency. Although these are currently incurable, genetic counselling and early detection can help patients lead almost normal lives. Furthermore, gene therapy experiments are in progress to correct the effects of the mutated gene in various severe Mendelian diseases.
Assoc Prof Eric Yap and his team focus on structural variation in the human genome, genomic analysis of complex diseases and rapid diagnostic technologies
However, most common diseases are caused not by single genes but multiple genes, each of which has only a small effect in predicting disease. Furthermore these disease genes interact with environmental factors around us, and using genetic tests as a prediction is complex. The severity and probability of a disease depends on the environment, lifestyle and diet. Some “bad” genes are only activated under certain circumstances. One example is the role of genetics in obesity. Genes controlling appetite and metabolism may predispose a person to gain weight easily. But this predisposition is only turned into actual kilos when lifestyle factors come into play. For example, someone predisposed to gaining weight easily, who eats a diet high in fat, may gain weight faster than someone without this predisposition. On the other hand, the same person living in a country plagued by famine might not even have the ability to gain any weight.
Other forms of environmental influences such as pollutants can also determine whether a person goes on to develop a disease. A common example is cigarette smoke. The chemicals in cigarette smoke, also known as mutagens, enter the body and directly interfere with a person’s DNA, resulting in mutated genes that may lead to death. You may not have inherited a gene from your parents that predisposes you to cancer, but lifestyle choices and eating habits over a lifetime can increase the risk of developing diseases.
Only a small number of diseases are caused purely by a single gene. Most common diseases however are a mixture of both genes and the environment.
By defining the genes and the various factors that affect them, scientists are one step closer to accurately predict the type of diseases that people may develop over time.
“With the advent of new molecular technologies it is now feasible to analyse multiple genes or even every one of the 20,000 genes that make up the human genome,” said Assoc Prof Yap. “These DNA sequencing and analysis methods have improved at an exponential rate, and allowed large scale research studies and whole genome testing for patients.”
Commercialising genetic testing
Genetic testing has been used in clinical settings for years, and with its wide potential has caught the eye of marketers who have banded together with scientists to commercialise and provide on-demand genetic testing to the public.
This affordable procedure is simple: order a DNA kit online, spit into a tube and send it back to the company where its scientists churn out results that you can look up online. These services cover a range of possible genetic markers, promising information on your ancestry to skin type, fitness or nutrition needs.
While genetic testing conducted by clinicians is crucial in a clinical setting, direct-to-consumer genetic testing is mostly marketed to people who are not necessarily ill, but simply curious to find out what their DNA sequence means.
But users should proceed with caution, as the science is still in its early stages and there are many things about genetics that are yet undiscovered. Thus, scientists and health practitioners advise caution when taking such tests, especially if the user is unsure about the results.
LKCMedicine Nanyang Assistant Professor Foo Jia Nee, whose work involves common and rare genetic variations responsible for several neurological diseases, said, “We [researchers] do advise to be cautious about these testing results as we need to ensure the patient is interpreting the results correctly or is getting the right information out of these companies.”
Test results could also deliver information that might be hard to handle, such as a predisposition to an incurable disease. Deputy Head of the National Healthcare Group Polyclinics (NHGP) Clinical Research Unit Dr Lee Eng Sing said, “To some individuals, it may be a very harsh and cruel fact, much like giving a death sentence way in advance.”
“Regardless of what your genetic information tells you, by taking better care of yourself, you’ll naturally be healthier,” added Asst Prof Foo.
These test results could also cause unnecessary dilemmas. Knowing she had an 87 per cent risk of developing breast cancer, Hollywood actress Angelina Jolie decided to undergo preventive double mastectomy. Such life-changing decisions require a good understanding of risk calculations and discussions with a professional.
“Undergoing such gene testing procedures to predict Breast Cancer risks (by testing BRCA1 and BRCA2 genes) where the health consequences are significant and the treatment options are complicated require the patient to understand her risks well, and genetic counselling to aid such major health decisions cannot be made simply over the internet,” Assoc Prof Yap added.
Are we ready for this?
With the technology and science on genetic testing widely available, the public now has access to information that may help them make informed choices about improving their health. This is a silver lining in an otherwise uncertain and early form of science. This “health blueprint” created through genetic testing could motivate people to exercise more and lead a healthier lifestyle. But even with a definitive diagnosis, people can be reluctant to make lifestyle changes.
“Most people aren’t willing to change their lifestyle,” said Dr Lee, “An example would be newly diagnosed diabetic patients who look at their sugar levels and remain in denial about their condition, simply because they are afraid of getting stigmatised by their friends and family members. Because of that, the majority of people will not follow lifestyle advice currently.”
As grim as that sounds, some people only find motivation to adopt a healthy lifestyle through witnessing first-hand the suffering of their diabetic family members, added Dr Lee.
But how then can we bring about change for the better? “Earlier and more accurate diagnosis is key,” said Professor of Cardiovascular Epidemiology at Imperial College London and LKCMedicine Visiting Professor John Chambers. “Genetic evaluation allows us to better identify people at risk of complex diseases from an early stage. In the case of diabetes and heart disease, this means we can then start treatment from an early stage, that may prevent the diseases ever developing”
Besides improving lifestyle and drug treatment, this data could also help scientists in planning new health services that provide quality counselling to patients and advise them on future health plans, especially for those who are not able to handle this kind of information well.
Assoc Prof Yap said, “Like going for a brain scan, genetic testing is not necessarily harmless. And not all of us are intellectually or emotionally able to handle that data well. An important part of this is the ability to understand the information and disease risks. So, equipping our patients with that knowledge to holistically deal with the implications of DNA testing is a health professional’s ethical responsibility.”
Genetic testing, as amazing as it sounds, is a double-edged sword after all.
The future of genetic testing
Having seen the potential of genetic testing, it may be that getting a complete health blueprint of your entire genome is possible in the near future.
In fact, several countries have already started collecting DNA samples from the public to map the population’s genetic sequences, pushing forward personalised medicine and collecting data to tackle diseases that are prevalent. The United Kingdom (UK) National Health Service began studying and collecting thousands of genetic codes from people across the nation to better diagnose and treat patients with rare diseases. Estonia is another country that has begun collecting a database of DNA samples out of its 1.3 million citizens. And Singapore too is making headway in this field.
“Singapore is also at the leading edge of efforts to unravel the genetic contribution to disease” says Prof Chambers. “Several large scale studies are underway, and Singapore scientists have made major contributions to advancing the field.”
Nevertheless there is still much to be learned and it will still be some years before routine genetic testing is mainstreamed into the public healthcare sector.
“I think potentially we will get there, but that requires more information from large patient cohorts with long-term follow-up,” said Asst Prof Foo. “That would really help us in the future, by using this genetic information to predict the health outcome of a person.”
However, many loopholes have to be closed to establish a safe and stable genetic testing environment in Singapore; from setting up a standardised database of genetic information to finding out if there is interest in the population in the first place. In addition, society needs to be ready for this kind of information. The public needs to be educated on genetic testing procedures, risk interpretations as well as how to make informed decisions. Genetic testing could also impact insurance and employment policies, preventing individuals with genetic disorders from benefiting from insurance coverage or miss out on employment opportunities, potentially opening the door to wide-spread discrimination.
As the science continues to evolve and more people become more concerned about their health and wellness, there will come a point when genetic testing could be streamlined into your nearest polyclinic or hospital. This could allow people to be more aware about their state of wellness and show them that a change in lifestyle could benefit both themselves and their family in the future. What may exist in story books and fairy tales now could possibly translate into reality.
“To improve the health at both an individual and the public health level in the future, understanding one’s genome as well as the mechanisms of diseases would help greatly,” said Assoc Prof Yap who has had his own DNA tested many times. “And I would say genome testing could help address the ultimate questions that concern each human: Who am I, how did I get here and where am I going?”